Ursolic Acid attenuates HMGB1-induced LOX-1 expression in vascular endothelial cells in vitro and inhibits atherogenesis in hypercholesterolemic mice in vivo

Ai-Wei Lee, Chun-Yao Huang, Chun-Ming Shih, Yi Wen Lin, Nai-Wen Tsao, Yung Hsiang Chen, Yu-Jia Chang, Nen-Chung Chang, Chi Yuan Li, Tsorng-Harn Fong, Chih Hao Nien, Feng-Yen Lin

Research output: Contribution to journalArticle

Abstract

Ursolic acid (UA), a triterpenoid compound found in plants, is used in both the human diet and in medicinal herbs and possesses a wide range of benefits, including antioxidative and anti-inflammatory effects. Additionally, UA may inhibit lipid absorption in pancreatic cells and enhance lipolysis in adipocytes. Oxidized LDL (oxLDL) acts as a major mediator of endothelium dysfunction, which mediates atherogenesis. Until now, we have not known what role UA plays in the absorption of oxidized LDL in vascular endothelial cells. Regardless of whether UA affects oxLDL uptake mediated by specific oxLDL receptors (such as lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), scavenger receptor expressed by endothelial cells (SREC), and scavenger receptor B1 (SR-B1)), it is unclear if UA acts on endothelial cells. However, high-mobility group box 1 (HMGB1) is known to accumulate in atherosclerotic lesions and mediates vascular inflammation, although the mechanisms are not understood. Therefore, in this study, human coronary artery endothelial cells (HCAECs) were used in vitro and hypercholesterolemic mice were used in vivo to investigate the effects and mechanisms of HMGB1 and UA on oxLDL uptake. The results demonstrated that HMGB1 enhances oxLDL uptake through induction of LOX-1 in HCAECs and hypercholesterolemic mice. In vitro data showed that exposing HMGB1- stimulated HCAECs to UA decreased the LOX-1-mediated absorption of oxLDL through a cyclooxygenase (COX)-2- related nitric oxide (NO) signaling pathway. Similarly, UA administration decreased LOX-1, but not SREC and SR-B1 expression, in HMGB1-treated hypercholesterolemic mice. These findings suggest that UA may be a potential therapeutic agent for hypercholesterolemia-induced atherosclerosis.

Original languageEnglish
Pages (from-to)317-329
Number of pages13
JournalImmunology, Endocrine and Metabolic Agents in Medicinal Chemistry
Volume12
Issue number4
DOIs
Publication statusPublished - 2012

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Atherosclerosis
Endothelial Cells
Scavenger Receptors
Coronary Vessels
Oxidized LDL Receptors
Class E Scavenger Receptors
ursolic acid
In Vitro Techniques
Lipolysis
Cyclooxygenase 2
Medicinal Plants
Hypercholesterolemia
Adipocytes
Endothelium
Blood Vessels
oxidized low density lipoprotein
Nitric Oxide
Anti-Inflammatory Agents
Diet
Inflammation

Keywords

  • Cyclooxygenase (COX)
  • High-mobility group box 1 (HMGB1)
  • Nitric oxide synthase (NOS)
  • Ursolic acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Pharmacology

Cite this

@article{43b8e776379543dcb8dd056c727b42a0,
title = "Ursolic Acid attenuates HMGB1-induced LOX-1 expression in vascular endothelial cells in vitro and inhibits atherogenesis in hypercholesterolemic mice in vivo",
abstract = "Ursolic acid (UA), a triterpenoid compound found in plants, is used in both the human diet and in medicinal herbs and possesses a wide range of benefits, including antioxidative and anti-inflammatory effects. Additionally, UA may inhibit lipid absorption in pancreatic cells and enhance lipolysis in adipocytes. Oxidized LDL (oxLDL) acts as a major mediator of endothelium dysfunction, which mediates atherogenesis. Until now, we have not known what role UA plays in the absorption of oxidized LDL in vascular endothelial cells. Regardless of whether UA affects oxLDL uptake mediated by specific oxLDL receptors (such as lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), scavenger receptor expressed by endothelial cells (SREC), and scavenger receptor B1 (SR-B1)), it is unclear if UA acts on endothelial cells. However, high-mobility group box 1 (HMGB1) is known to accumulate in atherosclerotic lesions and mediates vascular inflammation, although the mechanisms are not understood. Therefore, in this study, human coronary artery endothelial cells (HCAECs) were used in vitro and hypercholesterolemic mice were used in vivo to investigate the effects and mechanisms of HMGB1 and UA on oxLDL uptake. The results demonstrated that HMGB1 enhances oxLDL uptake through induction of LOX-1 in HCAECs and hypercholesterolemic mice. In vitro data showed that exposing HMGB1- stimulated HCAECs to UA decreased the LOX-1-mediated absorption of oxLDL through a cyclooxygenase (COX)-2- related nitric oxide (NO) signaling pathway. Similarly, UA administration decreased LOX-1, but not SREC and SR-B1 expression, in HMGB1-treated hypercholesterolemic mice. These findings suggest that UA may be a potential therapeutic agent for hypercholesterolemia-induced atherosclerosis.",
keywords = "Cyclooxygenase (COX), High-mobility group box 1 (HMGB1), Nitric oxide synthase (NOS), Ursolic acid",
author = "Ai-Wei Lee and Chun-Yao Huang and Chun-Ming Shih and Lin, {Yi Wen} and Nai-Wen Tsao and Chen, {Yung Hsiang} and Yu-Jia Chang and Nen-Chung Chang and Li, {Chi Yuan} and Tsorng-Harn Fong and Nien, {Chih Hao} and Feng-Yen Lin",
year = "2012",
doi = "10.2174/187152212803521048",
language = "English",
volume = "12",
pages = "317--329",
journal = "Anti-Infective Agents in Medicinal Chemistry",
issn = "2211-3525",
publisher = "Bentham Science Publishers",
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TY - JOUR

T1 - Ursolic Acid attenuates HMGB1-induced LOX-1 expression in vascular endothelial cells in vitro and inhibits atherogenesis in hypercholesterolemic mice in vivo

AU - Lee, Ai-Wei

AU - Huang, Chun-Yao

AU - Shih, Chun-Ming

AU - Lin, Yi Wen

AU - Tsao, Nai-Wen

AU - Chen, Yung Hsiang

AU - Chang, Yu-Jia

AU - Chang, Nen-Chung

AU - Li, Chi Yuan

AU - Fong, Tsorng-Harn

AU - Nien, Chih Hao

AU - Lin, Feng-Yen

PY - 2012

Y1 - 2012

N2 - Ursolic acid (UA), a triterpenoid compound found in plants, is used in both the human diet and in medicinal herbs and possesses a wide range of benefits, including antioxidative and anti-inflammatory effects. Additionally, UA may inhibit lipid absorption in pancreatic cells and enhance lipolysis in adipocytes. Oxidized LDL (oxLDL) acts as a major mediator of endothelium dysfunction, which mediates atherogenesis. Until now, we have not known what role UA plays in the absorption of oxidized LDL in vascular endothelial cells. Regardless of whether UA affects oxLDL uptake mediated by specific oxLDL receptors (such as lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), scavenger receptor expressed by endothelial cells (SREC), and scavenger receptor B1 (SR-B1)), it is unclear if UA acts on endothelial cells. However, high-mobility group box 1 (HMGB1) is known to accumulate in atherosclerotic lesions and mediates vascular inflammation, although the mechanisms are not understood. Therefore, in this study, human coronary artery endothelial cells (HCAECs) were used in vitro and hypercholesterolemic mice were used in vivo to investigate the effects and mechanisms of HMGB1 and UA on oxLDL uptake. The results demonstrated that HMGB1 enhances oxLDL uptake through induction of LOX-1 in HCAECs and hypercholesterolemic mice. In vitro data showed that exposing HMGB1- stimulated HCAECs to UA decreased the LOX-1-mediated absorption of oxLDL through a cyclooxygenase (COX)-2- related nitric oxide (NO) signaling pathway. Similarly, UA administration decreased LOX-1, but not SREC and SR-B1 expression, in HMGB1-treated hypercholesterolemic mice. These findings suggest that UA may be a potential therapeutic agent for hypercholesterolemia-induced atherosclerosis.

AB - Ursolic acid (UA), a triterpenoid compound found in plants, is used in both the human diet and in medicinal herbs and possesses a wide range of benefits, including antioxidative and anti-inflammatory effects. Additionally, UA may inhibit lipid absorption in pancreatic cells and enhance lipolysis in adipocytes. Oxidized LDL (oxLDL) acts as a major mediator of endothelium dysfunction, which mediates atherogenesis. Until now, we have not known what role UA plays in the absorption of oxidized LDL in vascular endothelial cells. Regardless of whether UA affects oxLDL uptake mediated by specific oxLDL receptors (such as lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), scavenger receptor expressed by endothelial cells (SREC), and scavenger receptor B1 (SR-B1)), it is unclear if UA acts on endothelial cells. However, high-mobility group box 1 (HMGB1) is known to accumulate in atherosclerotic lesions and mediates vascular inflammation, although the mechanisms are not understood. Therefore, in this study, human coronary artery endothelial cells (HCAECs) were used in vitro and hypercholesterolemic mice were used in vivo to investigate the effects and mechanisms of HMGB1 and UA on oxLDL uptake. The results demonstrated that HMGB1 enhances oxLDL uptake through induction of LOX-1 in HCAECs and hypercholesterolemic mice. In vitro data showed that exposing HMGB1- stimulated HCAECs to UA decreased the LOX-1-mediated absorption of oxLDL through a cyclooxygenase (COX)-2- related nitric oxide (NO) signaling pathway. Similarly, UA administration decreased LOX-1, but not SREC and SR-B1 expression, in HMGB1-treated hypercholesterolemic mice. These findings suggest that UA may be a potential therapeutic agent for hypercholesterolemia-induced atherosclerosis.

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KW - Nitric oxide synthase (NOS)

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